Glennon R A, Liebowitz S M, Anderson G M
J Med Chem. 1980 Mar;23(3):294-9. doi: 10.1021/jm00177a017.
Employing a rat fundus model, the serotonin (5-HT) receptor affinities of 45 phenalkylamine analogues were determined. Phenethylamine and phenylisopropylamine possess relatively low receptor affinities; in general, mono-, di-, and trimethoxylation enhance affinity. Of the disubstituted compounds, methoxyl groups at the 2 and 5 positions are optimal for imparting a high affinity. 4-Methylation, 4-ethylation and 4-bromination also enhance receptor affinity, while N,N-dimethylation of the terminal amine decreases affinity. alpha-Methylation of phenethylamines has little effect on affinity when racemates are examined. Introduction of a benzylic keto group can either increase or decrease affinity, depending upon the presence of other aromatic substituents. The most behaviorally active compounds were found to possess the highest 5-HT receptor affinities, while less active compounds were found to possess lower affinities.
利用大鼠眼底模型，测定了45种苯烷基胺类似物的血清素（5-HT）受体亲和力。苯乙胺和苯异丙胺具有相对较低的受体亲和力；一般来说，单甲氧基化、二甲氧基化和三甲氧基化会增强亲和力。在二取代化合物中，2位和5位的甲氧基对于赋予高亲和力是最佳的。4-甲基化、4-乙基化和4-溴化也会增强受体亲和力，而末端胺的N，N-二甲基化会降低亲和力。当检测外消旋体时，苯乙胺的α-甲基化对亲和力影响很小。引入苄基酮基可增加或降低亲和力，这取决于其他芳香取代基的存在。发现行为活性最高的化合物具有最高的5-HT受体亲和力，而活性较低的化合物则具有较低的亲和力。
